Dr. Vishaal Rajani
Faculty of Medicine
Co-Investigator: Dr. Qi Yuan
Dr. Rajani was awarded a 2021 ARC-NL Research Grant for his project entitled,
The Role of Calcium Signaling in Memory Impairment During Aging and in Alzheimer’s Disease (The Role of Hippocampal LTCCs in Synaptic Plasticity During Aging and in Pretangle Tau Pathology)
ARC-NL: What piqued your interest in this area of research?
My research is focused on synaptic plasticity, the reorganization of synaptic connections in the brain. These cellular changes are critical to normal processes such as learning and memory formation, and in long term modifications that occur during development and in disease pathophysiology. I became fascinated with the precise control and tight regulation of synaptic changes and hope to uncover the determinants underlying these changes that are key to neuronal function and dysfunction.
ARC-NL: Can you please provide a brief synopsis of your specific project?
Alzheimer’s disease affects over 747,000 aging adults in Canada, with devastating symptoms that include memory loss and cognitive impairment. New evidence reveals that the earliest sign of Alzheimer’s disease in humans is the appearance of an abnormal protein called “pretangle tau” in brainstem neurons, even at young ages. Pretangle tau is the precursor of tau tangles, one of the major signs of Alzheimer’s Disease in older brains. Over the years, pretangle tau spreads from the brainstem neurons to other brain structures, including the hippocampus, a critical brain site for memory formation.
In the hippocampus, calcium entry into the neuron is critical for memory formation. One of the pathways for calcium to enter the neuron is the L-type calcium channel. Once inside, calcium initiates the activation of downstream signalling cascades to produce long-lasting changes that are essential for long-term memory. During advanced aging, however, L-type calcium channels increase in number, leading to excessive calcium entry into the cell. This causes a disruption of normal calcium signalling, which is detrimental to memory formation. Similarly, excessive calcium entry and abnormal calcium signalling is observed during tau pathology in Alzheimer’s disease, leading to memory impairment and worsening of the aging-associated memory loss. We propose to study how L-type calcium channel dysfunction during aging and tau pathology impairs memory.
In our project, we will use sophisticated brain recording, imaging and behavioural methods to learn how calcium channel over-expression impacts memory formation during aging and use gene insertion techniques to express pretangle human tau in rat hippocampal neurons to learn how pretangles change neuron function over time. Our findings will help us to understand cellular mechanisms underlying memory impairment during aging and in Alzheimer’s disease pathophysiology and identify novel therapies to prevent negative changes to brain function.
ARC-NL: How did getting the support of the ARC-NL Research Grant assist you with your project?
The ARC-NL grant provides us with experimental support to develop new avenues in understanding cognitive dysfunction during aging and in Alzheimer’s disease. The support also allows us to present our findings at local, national, and international conferences, encouraging networking and raising awareness about age-related cognitive decline.
ARC-NL: How do you feel your research will benefit the aging population of Newfoundland and Labrador? Canada?
With improvements in health care, life expectancy has increased dramatically over time, leading to a growing number of aging individuals. Understanding the molecular underpinnings of age and Alzheimer’s related cognitive decline are becoming essential in early detection of dementia, and developing management therapies.